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Assaying Circuit Specific Regulation of Adult Hippocampal Neural Precursor Cells
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An epigenetic circuit controls neurogenic programs during neocortex development.

Andi Wang1, Junbao Wang1, Kuan Tian1

  • 1Frontier Science Center for Immunology and Metabolism, Medical Research Institute at School of Medicine, Department of Neurosurgery, Zhongnan Hospital of Wuhan University, College of Life Sciences, Wuhan University, Wuhan, China430071.

Development (Cambridge, England)
|January 12, 2022
PubMed
Summary

A novel epigenetic circuit involving long non-coding RNA (LncBAR) and BAF complex regulates neural progenitor cells. Loss of LncBAR impacts neocortical development and adult neurogenesis by altering Zbtb20 expression.

Keywords:
BAF complexIntermediate progenitor cellsLong non-coding RNANeocortexZBTB20

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Epigenetics

Background:

  • Intermediate progenitors (IPs) are crucial for neocortical neurogenesis.
  • Precise control of neurogenic programs is essential for proper brain development.

Purpose of the Study:

  • To characterize an epigenetic circuit controlling intermediate progenitor properties during neocortical development.
  • To elucidate the role of long non-coding RNA (LncBAR) in neurogenesis.

Main Methods:

  • Generation and analysis of LncBAR knockout mice.
  • Investigation of the interaction between LncBAR, BAF complex, and Zbtb20.
  • Assessment of neural progenitor cell cycle and neurogenesis in vivo and in vitro.

Main Results:

  • LncBAR knockout leads to altered neocortical neuron production and impaired adult neurogenesis.
  • LncBAR regulates Zbtb20 expression via the BAF chromatin-remodeling complex.
  • Zbtb20 overexpression rescues IP cell cycle defects in LncBAR-deficient precursors.

Conclusions:

  • LncBAR acts as a critical regulator of neocortical development and adult neurogenesis.
  • The LncBAR-BAF-Zbtb20 axis is a key epigenetic mechanism controlling neural progenitor cell fate and proliferation.